The treatment of chronic inflammatory disorders such as IBD represents a major medical challenge as they afflict several millions of persons. Its highest incidence is among developed countries and has been increasing steadily over the past 3 decades. Current therapies for IBD strongly need to be improved, a high percentage of patients (between 20 and 40%) being resistant to any forms of treatments, severe side effects and high costs being also associated to the currently available drugs (glucocorticoids and monoclonal antibody therapies). In addition, the mechanisms involved in the pathogenesis of IBD are not fully understood, and the development of more effective treatments or even cures for IBD depends upon better understanding the regulation of the inflammatory response. Several studies have demonstrated a crucial role for proteases in the maintenance of chronic inflammatory response of the gastrointestinal tract (GIT) [Vergnolle, N. 2005; Cenac, N. et al., 2007; Hyun, E., et al., 2008; Vergnolle, N., et al., 2004]. Therefore, endogenous protease inhibitors seem to be crucial to the control of intestinal inflammatory responses.
Based on this knowledge, the inventors propose that delivery of those protease inhibitors into the GIT, could be used for the treatment of an IBD and/or irritable Bowel syndrome (IBS).
The use of probiotics for the treatment of IBD has now been proposed for several years and different studies have reported some beneficial effects of these probiotic bacteria tested alone or in combination [Hedin, C. et al., 2007; Sartor, R. B. 2004]. The strategy of using recombinant non-pathogenic food-grade bacteria as delivery vehicles of anti-inflammatory molecules at the mucosal level has already been used to deliver the anti-inflammatory cytokine IL-10 [Steidler, L., et al., 2000]. Phase I clinical trials have demonstrated that orally given Lactococcus lactis strain expressing IL-10 cytokine, was safe as no serious side-effects occurred in those patients [Braat, H., et al., 2006]. However, the decreased disease activity in Crohn's disease patients treated with IL-10 recombinant L. lactis was somehow limited. This limited efficacy could be explained by the fact that IL-10 delivery has always been reported to have only discrete beneficial effects against the development of colitis [Braat, H. et al., 2003].
Citation or identification of any document in this application is not an admission that such document is available as prior art to the present invention.